tbuckley/cabot-search huggingface dataset:
Improving the Practice of Pain Management
Authors: June L. Dahl
Journal: JAMA (2000)

DERIVATIVES TO TREAT syphilis at the turn of the 20th century has been viewed as the dawn of the age of chemotherapy and rational drug design. 1When Ehrlich's personal secretary, Martha Marquardt, commented on his life, she reserved her most heartfelt praise not for his brilliance as a chemist but for his mission."Nothing on earth mattered to him except scientific research aimed to overcome suffering and disease." 1 These noble aims, however, were subject to priorities and agendas over which he had no control.English clinic staff viewed patients with syphilis as depraved sexual offenders, which adversely affected their compliance with treatment.In English colonies such as Uganda, eradicating syphilis was not a economic priority. 2,3 For these reasons, syphilis remained an explosive epidemic.Today, it is exciting to imagine the possibilities of biotechnological wonders like the human genome project, stem cells, and microarrays.But the priorities driving these efforts may be leading us astray.Michael R. Reich recently declared that the current drug development system, despite its "extraordinary research and development capacity," has led to "global inequities in health care." 4 He argued that the dependence on large profits from affluent countries created restrictively high drug prices and a penchant for developing drugs that target only the health problems of the wealthy.The solution, according to Reich, is the creation of incentives and reforms to refocus the global pharmaceutical industry on curing the most serious diseases rather than merely the most profitable ones.Articles in this issue explore how existing health management systems and technologies could be optimized "to overcome suffering and disease," often despite severe financial and logistical challenges.June Dahl argues for systematic changes to improve the medical management of pain-one of the most undertreated conditions for which highly effective drugs are readily available.Amit Etkin explains how the human genome data can be made clinically useful.Bret Ball and French Anderson outline how to overcome the major barriers that impede the application of gene therapy in the clinic.David Walton and Paul Farmer call for an end to the policies of negligence that have governed the treatment of multidrug-resistant tuberculosis in third world countries.Since Ehrlich's time, few of the principles of disease management seem to have changed."Rational drug design" still occurs largely through a process of large-scale screening techniques, moments of serendipity, and years of targeted research.Effective use of available therapies remains hampered by physicians who fail to prescribe drugs rationally.Pathogens may evolve to evade our therapies.But, at the current rate of progress in biotechnology, we may soon have the tools with which to address most of the world's diseases.However, how will we employ these tools and would Martha Marquardt approve?
Letter: C-Film as a contraceptive.
Authors: M V Smith, W Bounds
Journal: BMJ (1975)

enteral administration of hypertonic saline.Apparently the surgeon wished to use physio- logical saline (so-called 099% w/v) but pre- scribed "normal saline"; so the pharmacist made up normal saline (58-5 g/l), which is six times as strong, and this was given to the patient.This regrettable accident reinforces the need to abandon the use of "normal" (and of %) in medicine and in chemistry to de-
Recent Progress in Advanced Hydrogel‐Based Embolic Agents: From Rational Design Strategies to Improved Endovascular Embolization
Authors: Xiaohong Li, Muhammad Wajid Ullah, Basen Li, Hangrong Chen
Journal: Advanced Healthcare Materials (2023)

Abstract Transcatheter arterial embolization, a minimally invasive treatment to deliberately occlude the blood vessels, has become a safe and effective procedure for the management of vascular diseases and benign/malignant tumors. Particularly, hydrogel‐based embolic agents have garnered much attention because of their potential to address some of the limitations of clinically used embolic agents and can be rationally designed to impart more favorable characteristics or functions. In this review, the recent progress toward the development of polymer‐based hydrogels for effective endovascular embolization, including the in situ gelling hydrogels mediated by physically or chemically crosslinking, imageable hydrogels for intraprocedural and postprocedural feedback, use of hydrogels as the drug depot for local delivery of therapeutic drugs, hemostatic hydrogels inducing extrinsic or intrinsic coagulation of blood, stimuli‐responsive shape memory hydrogels as the smart embolization devices, and hydrogels incorporating external‐stimuli functional materials for multidisciplinary therapy, is systemically summarized. Moreover, the potential considerations of hydrogel‐based embolic agents confronted in therapeutic embolization are pointed out. Finally, the perspectives for the development of more effective embolic hydrogels are also highlighted.
Anti-CXCR2 antibody-coated nanoparticles with an erythrocyte-platelet hybrid membrane layer for atherosclerosis therapy
Authors: Rongzhong Huang, Lujun Zhang, Xingsheng Li, Fan Liu, Xiaoxiao Cheng, Haitao Ran, Zhigang Wang, Yongyong Li, Yuxing Feng, Liwen Liang, Wenhua Su, N.D. Melgiri, Yang Sun
Journal: Journal of Controlled Release (2023)
Microblading-transmitted Monkeypox (mpox) infection: fomites matter
Authors: Juan Luis Castaño-Fernández, Mercè Grau-Pérez
Journal: British Journal of Dermatology (2023)

Microblading is an increasingly popular semipermanent tattooing technique used for eyebrow pigmentation, involving the use of needles. During the 2022 mpox outbreak in Spain, a 47-year-old woman with no relevant medical history presented with a 10-day facial skin eruption.
Surface hydrolysis-designed AuNPs-zwitterionic-glucose as a novel tool for targeting macrophage visualization and delivery into infarcted hearts
Authors: Qianlong Wang, Tiantian Wang, Chonkit Lio, Xina Yu, Xiaoyi Chen, Lancong Liu, Youjiao Wu, Hui Huang, Linsen Qing, Pei Luo
Journal: Journal of Controlled Release (2023)
Quantitative analysis of urinary cytokines in food‐allergic and healthy individuals
Authors: Alexandra S. Lee, Ella S. Parsons, Iris Chang, Diane Dunham, R. Sharon Chinthrajah, Kari C. Nadeau
Journal: Allergy (2023)

Data S1: Figure S1: Table S1: Table S2: Table S3: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Therapeutic potential of salicylamide derivatives for combating viral infections
Authors: Jimin Xu, Yu Xue, Andrew A. Bolinger, Jun Li, Mingxiang Zhou, Haiying Chen, Hongmin Li, Jia Zhou
Journal: Medicinal Research Reviews (2023)

Abstract Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad‐spectrum antiviral agents. Salicylamide (2‐hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. In this review, we summarize the broad antiviral activities of salicylamide derivatives, the clinical progress, and the potential targets or mechanisms against different viral infections and highlight their therapeutic potential in combating the circulating and emerging viral infections in the future.
Nanoparticle‐Mediated STING Activation for Cancer Immunotherapy
Authors: Yongjuan Li, Xinyan Li, Jinmeng Yi, Yongjian Cao, Zhihai Qin, Zhiyuan Zhong, Weijing Yang
Journal: Advanced Healthcare Materials (2023)

Abstract As the first line of host defense against pathogenic infections, innate immunity plays a key role in antitumor immunotherapy. The cyclic GMP‐AMP synthase (cGAS)‐stimulator of interferon genes (STING) (cGAS‐STING) pathway has attracted much attention because of the secretion of various proinflammatory cytokines and chemokines. Many STING agonists have been identified and applied into preclinical or clinical trials for cancer immunotherapy. However, the fast excretion, low bioavailability, nonspecificity, and adverse effects of the small molecule STING agonists limit their therapeutic efficacy and in vivo application. Nanodelivery systems with appropriate size, charge, and surface modification are capable of addressing these dilemmas. In this review, the mechanism of the cGAS‐STING pathway is discussed and the STING agonists, focusing on nanoparticle‐mediated STING therapy and combined therapy for cancers, are summarized. Finally, the future direction and challenges of nano‐STING therapy are expounded, emphasizing the pivotal scientific problems and technical bottlenecks and hoping to provide general guidance for its clinical application.
<scp>PM<sub>2</sub></scp><sub>.5</sub> chemical constituents and allergic rhinitis: Findings from a prospective cohort study in China
Authors: Peng Jia, Chuanteng Feng, Tingting Ye, Ying Shao, Shujuan Yang
Journal: Allergy (2023)

Appendix S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Prognostic landscape of mitochondrial genome in myelodysplastic syndrome after stem-cell transplantation
Authors: Jing Dong, Christopher Staffi Buradagunta, Tao Zhang, Stephen Spellman, Yung-Tsi Bolon, Amy E. DeZern, Shahinaz M. Gadalla, H. Joachim Deeg, Aziz Nazha, Corey Cutler, Chao Cheng, Raul Urrutia, Paul Auer, Wael Saber
Journal: Journal of Hematology & Oncology (2023)

Abstract Despite mitochondrial DNA (mtDNA) mutations are common events in cancer, their global frequency and clinical impact have not been comprehensively characterized in patients with myelodysplastic neoplasia (also known as myelodysplastic syndromes, MDS). Here we performed whole-genome sequencing (WGS) on samples obtained before allogenic hematopoietic cell transplantation (allo-HCT) from 494 patients with MDS who were enrolled in the Center for International Blood and Marrow Transplant Research. We evaluated the impact of mtDNA mutations on transplantation outcomes, including overall survival (OS), relapse, relapse-free survival (RFS), and transplant-related mortality (TRM). A random survival forest algorithm was applied to evaluate the prognostic performance of models that include mtDNA mutations alone and combined with MDS- and HCT-related clinical factors. A total of 2666 mtDNA mutations were identified, including 411 potential pathogenic variants. We found that overall, an increased number of mtDNA mutations was associated with inferior transplantation outcomes. Mutations in several frequently mutated mtDNA genes ( e.g ., MT-CYB and MT-ND5 ) were identified as independent predictors of OS, RFS, relapse and/or TRM after allo-HCT. Integration of mtDNA mutations into the models based on the Revised International Prognostic Scores (IPSS-R) and clinical factors related to MDS and allo-HCT could capture more prognostic information and significantly improve the prognostic stratification efforts. Our study represents the first WGS effort in MDS receiving allo-HCT and shows that there may be clinical utility of mtDNA variants to predict allo-HCT outcomes in combination with more standard clinical parameters.
Biologically active secoiridoids: A comprehensive update
Authors: Zhongcan Peng, Jun He, Yungchi Cheng, Jiekun Xu, Weiku Zhang
Journal: Medicinal Research Reviews (2023)

Abstract Secoiridoids are natural products of cyclopentane monoterpene derivatives that are formed by splitting the rings of cyclomethene oxime compounds at C‐7 and C‐8, and only account for a small part of cyclic ether terpenoids. Because of the chemically active hemiacetal structure in their common basic skeleton, secoiridoids have a wide range of biological activities, such as neuroprotective, anti‐inflammatory, antidiabetic, hepatoprotective, and antinociceptive activities. Phenolic secoiridoids can also act against multiple molecular targets involved in human tumorigenesis, making them potentially valuable precursors for antitumor drug development. This review provides a detailed update, covering relevant discoveries from January 2011 to December 2020, about the occurrence, structural diversity, bioactivities, and synthesis of naturally occurring secoiridoids. We aimed to resolve the lack of extensive, specific, and thorough review of secoiridoids, as well as open new areas for pharmacological investigation and better drugs based on these compounds.
Dual IKZF2 and CK1α degrader targets acute myeloid leukemia cells
Authors: Sun-Mi Park, David K. Miyamoto, Grace Y.Q. Han, Mandy Chan, Nicole M. Curnutt, Nathan L. Tran, Anthony Velleca, Jun Hyun Kim, Alexandra Schurer, Kathryn Chang, Wenqing Xu, Michael G. Kharas, Christina M. Woo
Journal: Cancer Cell (2023)
Outersphere Approach to Increasing the Persistance of Oxygen‐Sensitive Europium(II)‐Containing Contrast Agents for Magnetic Resonance Imaging with Perfluorocarbon Nanoemulsions toward Imaging of Hypoxia
Authors: Jacob C. Lutter, Andrea L. Batchev, Caitlyn J. Ortiz, Alexander G. Sertage, Jonathan Romero, S. A. Amali S. Subasinghe, Steen E. Pedersen, Md Abul Hassan Samee, Robia G. Pautler, Matthew J. Allen
Journal: Advanced Healthcare Materials (2023)

Abstract Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of Eu(II) are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon‐nanoemulsion perfused with N 2 , forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon‐soluble complex of Eu(II). Conversion of the perfluorocarbon solution of Eu(II) into nanoemulsions results in observable differences between reduced and oxidized forms by magnetic resonance imaging both in vitro and in vivo. Oxidation in vivo occurrs over a period of ≈30 min compared to &lt;5 min for a comparable Eu(II)‐containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of Eu(II)‐containing complexes in vivo for the study of hypoxia.
A comparison of family physician and dermatologist topical corticosteroid prescriptions: A population-based cross-sectional study
Authors: Alexa C. Bowie, Mina Tadrous, Deva Thiruchelvam, Noah M. Ivers, Tanya Mohan, Karen Tu, Liisa Jaakkimainen, Aaron M. Drucker
Journal: Journal of the American Academy of Dermatology (2023)

BackgroundTopical corticosteroids (TCS) are commonly prescribed to treat inflammatory skin diseases, and appropriate prescription is necessary for treatment success.ObjectiveTo quantify differences between TCS prescribed by dermatologists at consultation and family physicians for patients treated for any skin condition.MethodsUsing administrative health data in Ontario, we included all Ontario Drug Benefit recipients who filled at least one TCS prescription from a dermatologist at consultation and a family physician in the year prior between January 2014 and December 2019. We estimated mean differences and 95% confidence intervals in amount (in grams) and potency between the index dermatologist prescription and the highest and most recent family physician prescription amounts and potencies in the preceding year using linear mixed-effect models.ResultsA total of 69,335 persons were included. The mean dermatologist amount was 34% larger than the highest amount and 54% larger than the most recent amount prescribed by family physicians. There were small but statistically significant differences in potency using established 7-category and 4-category potency classification systems.ConclusionsCompared to family physicians, dermatologists prescribed substantially larger amounts and similarly potent TCS at consultation. Further research is needed to determine the effect of these differences on clinical outcomes. Topical corticosteroids (TCS) are commonly prescribed to treat inflammatory skin diseases, and appropriate prescription is necessary for treatment success. To quantify differences between TCS prescribed by dermatologists at consultation and family physicians for patients treated for any skin condition. Using administrative health data in Ontario, we included all Ontario Drug Benefit recipients who filled at least one TCS prescription from a dermatologist at consultation and a family physician in the year prior between January 2014 and December 2019. We estimated mean differences and 95% confidence intervals in amount (in grams) and potency between the index dermatologist prescription and the highest and most recent family physician prescription amounts and potencies in the preceding year using linear mixed-effect models. A total of 69,335 persons were included. The mean dermatologist amount was 34% larger than the highest amount and 54% larger than the most recent amount prescribed by family physicians. There were small but statistically significant differences in potency using established 7-category and 4-category potency classification systems. Compared to family physicians, dermatologists prescribed substantially larger amounts and similarly potent TCS at consultation. Further research is needed to determine the effect of these differences on clinical outcomes.
Local contrastive loss with pseudo-label based self-training for semi-supervised medical image segmentation
Authors: Krishna Chaitanya, Ertunc Erdil, Neerav Karani, Ender Konukoglu
Journal: Medical Image Analysis (2023)

Supervised deep learning-based methods yield accurate results for medical image segmentation. However, they require large labeled datasets for this, and obtaining them is a laborious task that requires clinical expertise. Semi/self-supervised learning-based approaches address this limitation by exploiting unlabeled data along with limited annotated data. Recent self-supervised learning methods use contrastive loss to learn good global level representations from unlabeled images and achieve high performance in classification tasks on popular natural image datasets like ImageNet. In pixel-level prediction tasks such as segmentation, it is crucial to also learn good local level representations along with global representations to achieve better accuracy. However, the impact of the existing local contrastive loss-based methods remains limited for learning good local representations because similar and dissimilar local regions are defined based on random augmentations and spatial proximity; not based on the semantic label of local regions due to lack of large-scale expert annotations in the semi/self-supervised setting. In this paper, we propose a local contrastive loss to learn good pixel level features useful for segmentation by exploiting semantic label information obtained from pseudo-labels of unlabeled images alongside limited annotated images with ground truth (GT) labels. In particular, we define the proposed contrastive loss to encourage similar representations for the pixels that have the same pseudo-label/GT label while being dissimilar to the representation of pixels with different pseudo-label/GT label in the dataset. We perform pseudo-label based self-training and train the network by jointly optimizing the proposed contrastive loss on both labeled and unlabeled sets and segmentation loss on only the limited labeled set. We evaluated the proposed approach on three public medical datasets of cardiac and prostate anatomies, and obtain high segmentation performance with a limited labeled set of one or two 3D volumes. Extensive comparisons with the state-of-the-art semi-supervised and data augmentation methods and concurrent contrastive learning methods demonstrate the substantial improvement achieved by the proposed method. The code is made publicly available at https://github.com/krishnabits001/pseudo_label_contrastive_training.
Brain gene therapy with Trojan horse lipid nanoparticles
Authors: William M. Pardridge
Journal: Trends in Molecular Medicine (2023)

The COVID-19 mRNA vaccine was developed by the scalable manufacture of lipid nanoparticles (LNPs) that encapsulate mRNA within the lipid. There are many potential applications for this large nucleic acid delivery technology, including the delivery of plasmid DNA for gene therapy. However, gene therapy for the brain requires LNP delivery across the blood-brain barrier (BBB). It is proposed that LNPs could be reformulated for brain delivery by conjugation of receptor-specific monoclonal antibodies (MAbs) to the LNP surface. The MAb acts as a molecular Trojan horse to trigger receptor-mediated transcytosis (RMT) of the LNP across the BBB and subsequent localization to the nucleus for transcription of the therapeutic gene. Trojan horse LNPs could enable new approaches to gene therapy of the brain.
Effects of hyperoxemia in patients with sepsis – A post-hoc analysis of a multicentre randomized clinical trial
Authors: G. Catalisano, M. Ippolito, A. Blanda, J. Meessen, A. Giarratano, N. Todesco, V. Bonato, F. Restuccia, J. Montomoli, G. Fiore, G. Grasselli, P. Caironi, R. Latini, A. Cortegiani
Journal: Pulmonology (2023)

Administration of supplemental oxygen is a life-saving treatment in critically ill patients. Still, optimal dosing remains unclear during sepsis. The aim of this post-hoc analysis was to assess the association between hyperoxemia and 90-day mortality in a large cohort of septic patients.This is a post-hoc analysis of the Albumin Italian Outcome Sepsis (ALBIOS) randomized controlled trial (RCT). Patients with sepsis who survived the first 48 h since randomization were included and stratified into two groups according to their average PaO2 levels during the first 48 h (PaO2 0-48 h). The cut-off value was established at 100 mmHg (average PaO2 0-48 h >100 mmHg: hyperoxemia group; PaO2 0-48h≤100: normoxemia group). The primary outcome was 90-day mortality.1632 patients were included in this analysis (661 patients in the hyperoxemia group, 971 patients in the normoxemia group). Concerning the primary outcome, 344 (35.4%) patients in the hyperoxemia group vs. 236 (35.7%) in the normoxemia group had died within 90 days from randomization (p = 0.909). No association was found after adjusting for confounders (HR 0.87; CI [95%] 0.736-1.028, p = 0.102) or after excluding patients with hypoxemia at enrollment, patients with lung infection or including post-surgical patients only. Conversely, we found an association between lower risk of 90-day mortality and hyperoxemia in the subgroup including patients who had the lung as primary site of infection (HR 0.72; CI [95%] 0.565-0.918). Mortality at 28 days, ICU mortality, incidence of acute kidney injury, use of renal replacement therapy, days to suspension of vasopressor or inotropic agents, and resolution of primary and secondary infections did not differ significantly. Duration of mechanical ventilation and length of stay in ICU were significantly longer in patients with hyperoxemia.In a post-hoc analysis of a RCT enrolling septic patients, hyperoxemia as average PaO2>100 mmHg during the first 48 h was not associated with patients' survival.
Immune priming with avelumab and rituximab prior to R-CHOP in diffuse large B-cell lymphoma: the phase II AvR-CHOP study
Authors: Kate Manos, Geoffrey Chong, Colm Keane, Sze-Ting Lee, Charmaine Smith, Leonid Churilov, Joseph McKendrick, William Renwick, Piers Blombery, Melinda Burgess, Niles Elizabeth Nelson, Tineke Fancourt, Joanne Hawking, Wendi Lin, Andrew M. Scott, Allison Barraclough, Joel Wight, Andrew Grigg, Chun Yew Fong, Eliza A. Hawkes
Journal: Leukemia (2023)